To discover novel CB1 cannabinoid receptor antagonists as: a) potential cnadidates as medications for treatment of the ill effects of stimulants including cocaine and methamphetamine and other drugs of abuse;b) useful pharmacological and biochemical probes for studying the cannabinergic system. It has been shown that the selective CB1 antagonist SR141716A attenuates relapse induced by re-exposure to cocaine-associated cues or to cocaine itself. However, this compound was shown to exhibit undesirable side effects, was not approved in the US, and was withdrawn from clinical practice in Europe. These side effects may be chemotype-related, attributable to suboptimale ADME and/or its inverse antagonist profile. This contract seeks to develop a novel series of analogs based on a structurally distinct benzhydryloxyazetidine prototype.
